Creatine Deficiency, Uptake and Breakdown Studied in Brain and Muscle of Arginine:Glycine Amidinotransferase Deficient Mice

Christine Nabuurs¹, Martijn Romeijn¹, Andor Veltien¹, Hermien Kan¹, Dirk Isbrandt², Arend Heerschap¹

Arginine:glycine amidinotransfererase is an essential step in the biosynthesis of creatine. Inborn errors of genes for this enzyme lead to creatine deficiency syndromes, which can be treated by oral Cr intake. However, the rates of Cr uptake in different tissue types have not been assessed. In this study we determined total Cr uptake and breakdown in muscle and brain of mutant mice with AGAT deficiency by means of a longitudinal 1H MRS study. Muscle tissue demonstrated remarkably fast uptake, already after 1 day the levels of tCr were comparable to that of wildtypes. In contrast, uptake in brain was much slower reaching normal levels at ~20 days of treatment. These results suggest that the blood-brain-barrier significantly delays uptake of Cr in brain.